We plan to synthesize a number of beta-lactams which have two or more of the special structural features of the small number of known beta-lactamase inhibitors. A majority of the projected compounds will be beta-lactams fused to a five-membered ring system with or without hetero atoms in this ring. The interaction of these compounds with pure beta-lactamases will be studied to test their effectiveness as beta-lactamase inhibitors. On the basis of structure activity relationship deduced from this study, attempts will be made to design antibiotics with built in anti-beta-lactamase activity. Stereospecific synthetic methods will be explored for the preparation of target beta-lactams. These methods can be expected to provide easy access to beta-lactams labeled with stable isotopes for NMR studies on beta-lactamase/inhibitor interaction. The proposed research can be expected to generate new information of interest to medical chemists, synthetic chemists and biochemists.